The CIPRA-SA program project grant is in the fifth year of funding under the grant U19 AI53217-05. This application aims to justify the request for funding extension by demonstrating the successes of the program to date, and re-emphasizing the relevance and importance of all the research projects. Overall the program consists of an Administrative Core A, responsible for all financial, human resources, quality assurance, data management and statistics. Core B is responsible for all laboratory support, laboratory quality assurance and the development of appropriate affordable laboratory assays for HIV and TB. These cores supports the implementation of the research projects: (1) "Safeguard the Household" A Study of HIV Antiretroviral Therapy Treatment Strategies Appropriate for a Resource Poor Country (n=840) (2) "CHER" A phase III randomized open label trial to evaluate strategies for providing antiretroviral therapy to infants shortly after primary infection in resource poor setting (n=375), (3) A study of the effects of antiretroviral therapy on rates and transmission of tuberculosis (n=180), (4) Evaluation of quantitative and qualitative antibody responses to Streptococcus pneumoniae and Haemophilus influenzae type b conjugate vaccines amongst HIV-1-exposed-infected children that are receiving vs. those not receiving antiretroviral therapy, as well as among HIV-1-exposed-uninfected children and HIV-1-unexposed-uninfected children (n=560), (5) .Innovative and affordable laboratory diagnosis and monitoring for HIV. The program has successfully completed the development of site establishment for all the sites, laboratory establishment, and secured support to provide antiretroviral therapy. With all regulatory approvals in place between January 2005 and April 2005, recruitment of patients was initiated. Enrollment and accrual into all the studies planned in the program have been completed. Overall the success of the program is facilitated by the inter-digitation of the projects. Project 1 has established a large cohort of 840 patients, providing a unique opportunity for linked studies in Projects 3 and 5 for collection of epidemiologic data and laboratory data. HIV positive children recruited in project 2 are co-enrolled in project 4. Overall the administrative and laboratory cores efficiently support the research activities. In addition the statistics and data management core supports the activities of a number of other CIPRA programs internationally. The CIPRA-SA research program will answer relevant and topical questions about appropriate strategies for the provision of anti-retrovirals to adults and children in low-resource settings, the impact of ART on TB and the use of pneumococcal vaccines in HIV infected and exposed children, which are of major public health significance.